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The role of sentrin-specific protease 2 substrate recognition in TGF-β-induced tumorigenesis.
- Source :
-
Scientific reports [Sci Rep] 2018 Jun 28; Vol. 8 (1), pp. 9786. Date of Electronic Publication: 2018 Jun 28. - Publication Year :
- 2018
-
Abstract
- Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-β signals into the nuclei. Although many cellular factors are involved in TGF-β induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-β. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-β repression. The SENP2 <superscript>363~400</superscript> segment is critical for TGF-β-induced cell migration, which is correlated with SENP2 <superscript>363~400</superscript> deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-β induced cancer cell migration.
- Subjects :
- Cell Movement
Humans
Protein Binding
Signal Transduction drug effects
Smad4 Protein metabolism
Spheroids, Cellular metabolism
Spheroids, Cellular pathology
Substrate Specificity
Sumoylation
Transforming Growth Factor beta
Carcinogenesis metabolism
Carcinogenesis pathology
Cysteine Endopeptidases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29955155
- Full Text :
- https://doi.org/10.1038/s41598-018-28103-8